Inhibition of oncogene STAT3 phosphorylation by a prolactin antagonist, hPRL-G129R, in T-47D human breast cancer cells

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Published on Friday, 07 June 2019

Abstract

We have previously demonstrated that a hPRL antagonist (hPRL-G129R) was able to inhibit PRL induced breast cancer cell proliferation through induction of apoptosis.

In the present study, we test the hypothesis that the inhibitory effect of hPRL-G129R in breast cancer cells occurs, at least in part, through the inhibition of oncogene STAT3 activation.

We first demonstrated that STAT5 and STAT3 could be activated by either hGH or hPRL in T-47D breast cancer cells. Although the patterns of STAT5 activation by hGH and hPRL are similar, we observed a nearly 10-fold greater efficacy of hPRL in STAT3 activation as compared to that of hGH. More importantly, we have demonstrated that activation of STAT3 by hPRL could be inhibited by hPRL-G129R. Since T-47D cells coexpress GHR and PRLR, an attempt was made to dissect the molecular events mediated through hGHR or hPRLR using mouse L-cells expressing a single population of receptors (hGHR or hPRLR). To our surprise, only STAT5, not STAT3 phosphorylation was observed in these L-cells.

In conclusion, our results suggest that: a) STAT3 is preferably activated through hPRLR in T-47D cells; b) hPRL-G129R is effective in inhibiting STAT3 phosphorylation; and c) the mechanism of STAT3 activation is different from that of STAT5.

 

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